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Publication Abstract from PubMed

Structural roles of loop regions are frequently overlooked in proteins. Nevertheless, they may be key players in the definition of protein topology and in the self-assembly processes occurring through domain swapping. We here investigate the effects on structure and stability of replacing the loop connecting the last two beta-strands of RNase A with the corresponding region of the more thermostable Onconase. The crystal structure of this chimeric variant (RNaseA-ONC) shows that its terminal loop size better adheres to the topological rules for the design of stabilized proteins, proposed by Baker and coworkers [43]. Indeed, RNaseA-ONC displays a thermal stability close to that of RNase A, despite the lack of Pro at position 114, which, due to its propensity to favor a cis peptide bond, has been identified as an important stabilizing factor of the native protein. Accordingly, RNaseA-ONC is significantly more stable than RNase A variants lacking Pro114; RNaseA-ONC also displays a higher propensity to form oligomers in native conditions when compared to either RNase A or Onconase. This finding demonstrates that modifications of terminal loops should to be carefully controlled in terms of size and sequence to avoid unwanted and/or potentially harmful aggregation processes.

Structure, stability and aggregation propensity of a Ribonuclease A-Onconase chimera.,Esposito L, Donnarumma F, Ruggiero A, Leone S, Vitagliano L, Picone D Int J Biol Macromol. 2019 Apr 23. pii: S0141-8130(19)31077-3. doi:, 10.1016/j.ijbiomac.2019.04.164. PMID:31026530^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.